TAFI inhibitors and their use to treat pulmonary fibrosis

Abstract

The invention relates to TAFI inhibitors and their use to treat pulmonary fibrosis.

1 . A method of treating pulmonary fibrosis comprising administering a therapeutically effective amount of a compound of formula (I) to a patient in need thereof:  
     
       
         
         
             
             
         
       
       wherein:  
       R 1  is hydrogen, alkyl, alkenyl, aralkyl, or aralkenyl;  
       R 2  is —SH, —S—C(O)—R 8 , —P(O)(OR 5 ) 2 , —P(O)(OR 5 )R 6 , —P(O)(OR 5 )—R 7 —N(R 6 ) 2 , —P(O)(OR 5 )—R 7 —C(O)—R 8 , —P(O)(OR 5 )—R 7 —N(R 5 )—C(O)OR 8 , —P(O)(OR 5 )—R 7 —N(R 5 )—C(O)—R 7 —N(R 5 )—C(O)OR 8 , —P(O)(OR 5 )—R 7 —N(R 5 )—S(O) 2 —R 9 , or —P(O)(OR 5 )—R 7 —N(R 5 )—C(S)—N(R 6 ) 2 ;  
       R 3  is tetrazole, —C(O)OR 6 , —C(O)O—R 7 —OC(O)R 5 , —S(O)OR 5 , —S(O) 2 OR 5 , —P(O)(OR 5 ) 2 , —P(O)(OR 5 )R 6 , or —B(OR 5 ) 2 ;  
       R 4  is aryl optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, haloalkoxy, mercapto, alkylthio, phenyl, cycloalkyl, nitro, cyano, —OR 6 , —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 , —R 7 —N(R 6 )—C(O)OR 8 , —N(R 6 )—C(O)—R 6 , —R 7 —N(R 6 )—C(O)—R 6 , —C(O)—N(R 6 ) 2 , —C(O)—R 7 —N(R 6 ) 2 , —N(R 5 )—C(NR 5 )—N(R 5 ) 2 , —N(R 5 )—C(O)—N(R 6 ) 2  and —N(R 5 )—C(O)—R 7 —N(R 6   2 );  
       or R 4  is N-heterocyclyl wherein a carbon atom in the N-heterocyclyl may be optionally substituted by alkyl, halo, nitro, cyano, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 , —R 7 —N(R 6 )—C(O)OR 8 , —N(R 6 )—C(O)—R 6 , —R 7 —N(R 6 )—C(O)—R 6 , —C(O)—N(R 6 ) 2 , —C(O)—R 7 —N(R 6 ) 2 , —N(R 5 )—C(NR 5 )—N(R 5 ) 2 , —N(R 5 )—C(O)—N(R 6 ) 2  or —N(R 5 )—C(O)—R 7 —N(R 6   2 ), or wherein a nitrogen atom in the N-heterocyclyl may be optionally substituted by —C(NR 5 )—N(R 5 ) 2 , —C(NR 5 )—R 6 , —C(O)—N(R 6 ) 2  or —C(O)—R 7 —N(R 6 ) 2 ;  
       each R 5  is independently hydrogen, alkyl or aralkyl;  
       each R 6  is independently hydrogen, alkyl, alkenyl, alkynyl, aryl, aralkyl or aralkenyl;  
       each R 7  is independently cycloalkylene (optionally substituted by alkyl), a straight or branched alkylene chain (optionally substituted by hydroxy, mercapto, alkylthio, aryl, cycloalkyl, —N(R 6 ) 2 , —C(O)OR 6 , or —C(O)N(R 6 ) 2 ), or a straight or branched alkenylene chain (optionally substituted by hydroxy, mercapto, alkylthio, aryl, cycloalkyl, —N(R 6 ) 2 , —C(O)OR 6 , or —C(O)N(R 6 ) 2 );  
       each R 8  is independently alkyl, alkenyl, aryl, aralkyl or aralkenyl; and  
       R 9  is —R 7  N(R 6 )C(O)OR 8 , haloalkyl, alkyl (optionally substituted by hydroxy, alkoxy, aralkoxy, haloalkoxy, cyano, nitro, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), alkenyl (optionally substituted by hydroxy, alkoxy, haloalkoxy, cyano, nitro, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), aryl (optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR , —C(O)N(R 6 ) 2  or —N(R 5 )C(O)R 6 ), aralkyl (wherein the aryl group is optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), aralkenyl (wherein the aryl group is optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), or N-heterocyclyl (optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 );  
       provided that when R 3  is —C(O)OH or when R 4  is a substituted aryl or substituted N-heterocyclyl, R 2  can not be —P(O)(OR 5 )—R 7 —N(H)—C(O)OR 8  or —P(O)(OR 5 )—R 7 —N(H)—C(O)—R 7 —N(R 5 )—C(O)OR 8 ;  
       as a single stereoisomer, a mixture of stereoisomers, or as a racemic mixture of stereoisomers; or a pharmaceutically acceptable salt thereof.  
     
   
   
       2 . The method of  claim 1  wherein: 
 R 1  is hydrogen;    R 2  is —SH or —S—C(O)—R 8 ;    R 3  is tetrazole, —C(O)OR 6  or —C(O)O—R 7 —OC(O)R 5 ;    R 4  is aryl optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, nitro, cyano, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 , —R 7 —N(R 6 )—C(O)OR 8 , —N(R 6 )—C(O)—R 6 , —R 7 —N(R 6 )—C(O)—R 6 , —C(O)—N(R 6 ) 2 , —C(O)—R 7 —N(R 6 ) 2 , —N(R 5 )—C(NR 5 )—N(R 5 ) 2 , —N(R 5 )—C(O)—N(R 6 ) 2  and —N(R 5 )—C(O)—R 7 —N(R 6   2 );    or R 4  is N-heterocyclyl wherein a carbon atom in the N-heterocyclyl may be optionally substituted by alkyl, halo, nitro, cyano, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 , —R 7 —N(R 6 )—C(O)OR 8 , —N(R 6 )—C(O)—R 6 , —R 7 —N(R 6 )—C(O)—R 6 , —C(O)—N(R 6 ) 2 , —C(O)—R 7 —N(R 6 ) 2 , —N(R 5 )—C(NR 5 )—N(R 5 ) 2 , —N(R 5 )—C(O)—N(R 6 ) 2  or —N(R 5 )—C(O)—R 7 —N(R 6   2 ), or wherein a nitrogen atom in the N-heterocyclyl may be optionally substituted by —C(NR 5 )—N(R 5 ) 2 , —C(NR 5 )—R 6 , —C(O)—N(R 6 ) 2  or —C(O)—R 7 —N(R 6 ) 2 ;    each R 5  is independently hydrogen, alkyl or aralkyl;    each R 6  is independently hydrogen, alkyl, alkenyl, alkynyl, aryl, aralkyl or aralkenyl;    each R 7  is independently a straight or branched alkylene chain optionally substituted by hydroxy, mercapto, alkylthio, aryl, cycloalkyl, —N(R 6 ) 2 , —C(O)OR 6 , or —C(O)N(R 6 ) 2 ; and    each R 8  is independently alkyl, alkenyl, aryl, aralkyl or aralkenyl.    
   
   
       3 . The method of  claim 2  wherein: 
 R 1  is hydrogen;    R 2  is —SH or —S—C(O)—R 8 ;    R 3  is —C(O)OR 6 ;    R 4  is aryl optionally substituted by one or more substituents selected from the group consisting of halo, nitro, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2  and —N(R 5 )—C(NR 5 )—N(R 5 ) 2 ;    each R 5  is independently hydrogen, alkyl or aralkyl;    each R 6  is independently hydrogen, alkyl, aryl or aralkyl;    R 7  is a straight or branched alkylene chain; and    R 8  is alkyl, alkenyl, aryl, aralkyl or aralkenyl.    
   
   
       4 . The method of  claim 3  wherein the compound of formula (I) is selected from the group consisting of: 
 2-(4-guanidinophenyl)-3-mercaptopropanoic acid;    2-(3-guanidinophenyl)-3-mercaptopropanoic acid;    2-(3-aminophenyl)-3-mercaptopropanoic acid; and    2-(2-chloro-5-guanidinophenyl)-3-mercaptopropanoic acid.    
   
   
       5 . The method of  claim 2  wherein: 
 R 1  is hydrogen;    R 2  is —SH, or —S—C(O)—R 8 ;    R 3  is —C(O)OR 6 ;    R 4  is 3(4)-piperidinyl wherein the nitrogen atom in the piperidinyl radical is optionally substituted by —C(NR 5 )—N(R 5 ) 2 , —C(NR 5 )—R 6 , —C(O)—N(R 6 ) 2  or —C(O)—R 7 —N(R 6 ) 2 ;    each R 5  is independently hydrogen, alkyl or aralkyl;    each R 6  is independently hydrogen, alkyl, aryl or aralkyl;    R 7  is a straight or branched alkylene chain optionally substituted by hydroxy, mercapto, alkylthio, aryl, cycloalkyl, —N(R 6 ) 2 , —C(O)OR 6 , or —C(O)N(R 6 ) 2 ; and    R 8  is independently alkyl, alkenyl, aryl, aralkyl or aralkenyl.    
   
   
       6 . The method of  claim 5  wherein the compound of formula (I) is selected from the group consisting of: 
 2-(piperidin-4-yl)-3-mercaptopropanoic acid;    2-(1-amidinopiperidin-4-yl)-3-mercaptopropanoic acid;    2-(1-(1-iminoethyl)piperidin4-yl)-3-mercaptopropanoic acid;    2-(1-(aminomethylcarbonyl)piperidin4-yl)-3-mercaptopropanoic acid;    2-(piperidin-3-yl)-3-mercaptopropanoic acid; and    2-(1-amidinopiperidin-3-yl)-3-mercaptopropanoic acid.    
   
   
       7 . The method of  claim 1  wherein: 
 R 1  is hydrogen;    R 2  is —P(O)(OR 5 ) 2 , —P(O)(OR 5 )R 6  or —P(O)(OR 5 )—R 7 —C(O)—R 8 ;    R 3  is tetrazole, —C(O)OR 6 , or —C(O)O—R 7 —OC(O)R 5 ;    R 4  is aryl optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, nitro, cyano, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 , —R 7 —N(R 6 )—C(O)OR 8 , —N(R 6 )—C(O)—R 6 , —R 7 —N(R 6 )—C(O)—R 6 , —C(O)—N(R 6 ) 2 , —C(O)—R 7 —N(R 6 ) 2 , —N(R 5 )—C(NR 5 )—N(R 5 ) 2 , —N(R 5 )—C(O)—N(R 6 ) 2  and —N(R 5 )—C(O)—R 7 —N(R 6   2 );    or R 4  is N-heterocyclyl wherein a carbon atom in the N-heterocyclyl may be optionally substituted by alkyl, halo, nitro, cyano, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 , —R 7 —N(R 6 )—C(O)OR 8 , —N(R 6 )—C(O)—R 6 , —R 7 —N(R 6 )—C(O)—R 6 , —C(O)—N(R 6 ) 2 , —C(O)—R 7 —N(R 6 ) 2 , —N(R 5 )—C(NR 5 )—N(R 5 ) 2 , —N(R 5 )—C(O)—N(R 6 ) 2  or —N(R 5 )—C(O)—R 7 —N(R 6   2 ), or wherein a nitrogen atom in the N-heterocyclyl may be optionally substituted by —C(NR 5 )—N(R 5 ) 2 , —C(NR 5 )—R 6 , —C(O)—N(R 6 ) 2  or —C(O)—R 7 —N(R 6 ) 2 ;    each R 5  is independently hydrogen, alkyl or aralkyl;    each R 6  is independently hydrogen, alkyl, alkenyl, alkynyl, aryl, aralkyl or aralkenyl;    each R 7  is independently a straight or branched alkylene chain optionally substituted by hydroxy, mercapto, alkylthio, aryl, cycloalkyl, —N(R 6 ) 2 , —C(O)OR 6 , or —C(O)N(R 6 ) 2 ; and    each R 8  is independently alkyl, alkenyl, aryl, aralkyl or aralkenyl.    
   
   
       8 . The method of  claim 7  wherein: 
 R 1  is hydrogen;    R 2  is —P(O)(OR 5 ) 2 , —P(O)(OR 5 )R 6  or —P(O)(OR 5 )—R 7 —C(O)—R 8 ;    R 3  is —C(O)OR 6 ;    R 4  is aryl optionally substituted by one or more substituents selected from the group consisting of halo, nitro, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2  and —N(R 5 )—C(NR 5 )—N(R 5 ) 2 ;    each R 5  is independently hydrogen, alkyl or aralkyl;    each R 8  is independently hydrogen, alkyl, aryl or aralkyl;    each R 7  is independently a straight or branched alkylene chain optionally substituted by aryl, —N(R 6 ) 2  or —C(O)OR 6 ; and    R 8  is alkyl, alkenyl, aryl, aralkyl or aralkenyl.    
   
   
       9 . The method of  claim 8  wherein the compound of formula (I) is selected from the group consisting of: 
 2-(3-guanidinophenyl)-3-phosphonopropanoic acid;    2-(3-aminophenyl)-3-((phenyl)(hydroxy)phosphinoyl)propanoic acid;    2-(3-aminophenyl)-3-((4-phenylbutyl)(hydroxy)phosphinoyl)propanoic acid;    2-(3-aminophenyl)-3-((pentyl)(hydroxy)phosphinoyl)propanoic acid;    2-(3-guanidinophenyl)-3-((phenyl)(hydroxy)phosphinoyl)propanoic acid;    2-(3-guanidinophenyl)-3-((4-phenylbutyl)(hydroxy)phosphinoyl)propanoic acid;    2-(3-guanidinophenyl)-3-((pentyl)(hydroxy)phosphinoyl)propanoic acid;    2-(3-guanidinophenyl)-3-((4-methylpentyl)(hydroxy)phosphinoyl)propanoic acid;    2-(3-guanidinophenyl)-3-((3-phenylpropyl)(hydroxy)phosphinoyl)propanoic acid;    2-(3-guanidinophenyl)-3-((3-phenylprop-2-enyl)(hydroxy)phosphinoyl)propanoic acid;    2-(3-guanidinophenyl)-3-((phenylmethyl)(hydroxy)phosphinoyl)propanoic acid;    2-(3-guanidinophenyl)-3-((pentyl)(hydroxy)phosphinoyl)propanoic acid methyl ester;    2-(3-guanidinophenyl)-3-((ethyl)(hydroxy)phosphinoyl)propanoic acid;    2-(3-guanidinophenyl)-3-((2-phenylethyl)(hydroxy)phosphinoyl)propanoic acid; and    2-(3-guanidinophenyl)-3-((2-(methylcarbonyl)ethyl)(hydroxy)phosphinoyl)propanoic acid.    
   
   
       10 . The method of  claim 1  wherein: 
 R 1  is hydrogen;    R 2  is —P(O)(OR 5 )—R 7 —N(R 5 )—C(O)OR 8 ;    R 3  is —C(O)OR 6  (where R 6  is alkyl, aryl or aralkyl);    R 4  is aryl optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, nitro, cyano, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 , —R 7 —N(R 6 )—C(O)OR 8 , —N(R 6 )—C(O)—R 6 , —R 7 —N(R 6 )—C(O)—R 6 , —C(O)—N(R 6 ) 2 , —C(O)—R 7 —N(R 6 ) 2 , —N(R 5 )—C(NR 5 )—N(R 5 ) 2 —N(R 5 )—C(O)—N(R 6 ) 2  and —N(R 5 )—C(O)—R 7 —N(R 6   2 ) where each R 6  is independently hydrogen, alkyl, aryl or aralkyl;    each R 5  is independently hydrogen, alkyl or aralkyl;    each R 7  is a straight or branched alkylene chain optionally substituted by aryl, —N(R 6 ) 2  or —C(O)OR 6 ; and    each R 8  is independently alkyl, alkenyl, aryl, aralkyl or aralkenyl.    
   
   
       11 . The method of  claim 10  wherein the compound of formula (I) is selected from the group consisting of: 
 2-(3-(t-butoxycarbonylamino)methylphenyl)-3-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)propanoic acid t-butyl ester; and    2-(3-(t-butoxycarbonylamino)methylphenyl)-3-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(ethoxy)phosphinoyl)propanoic acid t-butyl ester.    
   
   
       12 . The method of  claim 1  wherein: 
 R 1  is hydrogen;    R 2  is —P(O)(OR 5 )—R 7 —N(R 6 ) 2  or —P(O)(OR 5 )—R 7 —N(R 5 )—C(S)—N(R 6 ) 2 ;    R 3  is tetrazole, —C(O)OR 6 , or —C(O)O—R 7 —OC(O)R 5 ;    R 4  is aryl optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, nitro, cyano, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 , —R 7 —N(R 6 )—C(O)OR 8 , —N(R 6 )—C(O)—R 6 , —R 7 —N(R 6 )—C(O)—R 6 , —C(O)—N(R 6 ) 2 , —C(O)—R 7 —N(R 6 ) 2 , —N(R 5 )—C(NR 5 )—N(R 5 ) 2 , —N(R 5 )—C(O)—N(R 6 ) 2  and —N(R 5 )—C(O)—R 7 —N(R 6   2 );    each R 5  is independently hydrogen, alkyl or aralkyl;    each R 6  is independently hydrogen, alkyl, alkenyl, alkynyl, aryl, aralkyl or aralkenyl;    each R 7  is a straight or branched alkylene chain optionally substituted by hydroxy, mercapto, alkylthio, aryl, cycloalkyl, —N(R 6 ) 2 , —C(O)OR 6 , or —C(O)N(R 6 ) 2 ; and    each R 8  is independently alkyl, alkenyl, aryl, aralkyl or aralkenyl.    
   
   
       13 . The method of  claim 12  wherein the compound of formula (I) is selected from the group consisting of: 
 2-(3-(t-butoxycarbonylamino)methylphenyl)-3-((1-amino-2-methylpropyl)(hydroxy)-phosphinoyl)propanoic acid t-butyl ester; and    2-(3-(t-butoxycarbonylamino)methylphenyl)-3-((1-amino-2-methylpropyl)(ethoxy)-phosphinoyl)propanoic acid t-butyl ester.    
   
   
       14 . The method of  claim 1  wherein: 
 R 1  is hydrogen;    R 2  is —P(O)(OR 5 )—R 7 —N(R 5 )—S(O) 2 —R 9 ;    R 3  is tetrazole, —C(O)OR 6 , or —C(O)O—R 7 —OC(O)R 5 ;    R 4  is aryl optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, nitro, cyano, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 , —R 7 —N(R 6 )—C(O)OR 8 , —N(R 6 )—C(O)—R 6 , —R 7 —N(R 6 )—C(O)—R 6 , —C(O)—N(R 6 ) 2 , —C(O)—R 7 —N(R 6 ) 2 , —N(R 5 )—C(NR 5 )—N(R 5 ) 2 , —N(R 5 )—C(O)—N(R 6 ) 2  and —N(R 5 )—C(O)—R 7 —N(R 6   2 );    or R 4  is N-heterocyclyl wherein a carbon atom in the N-heterocyclyl may be optionally substituted by alkyl, halo, nitro, cyano, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 , —R 7 —N(R 6 )—C(O)OR 8 , —N(R 6 )—C(O)—R 6 , —R 7 —N(R 6 )—C(O)—R 6 , —C(O)—N(R 6 ) 2 , —C(O)—R 7 —N(R 6 ) 2 , —N(R 5 )—C(NR 5 )—N(R 5 ) 2 , —N(R 5 )—C(O)—N(R 6 ) 2  or —N(R 5 )—C(O)—R 7 —N(R 6   2 ), or wherein a nitrogen atom in the N-heterocyclyl may be optionally substituted by —C(NR 5 )—N(R 5 ) 2 , —C(NR 5 )—R 6 , —C(O)—N(R 6 ) 2  or —C(O)—R 7 —N(R 6 ) 2 ;    each R 5  is independently hydrogen, alkyl or aralkyl;    each R 6  is independently hydrogen, alkyl, alkenyl, alkynyl, aryl, aralkyl or aralkenyl;    each R 7  is independently cycloalkylene (optionally substituted by alkyl), a straight or branched alkylene chain (optionally substituted by hydroxy, mercapto, alkylthio, aryl, cycloalkyl, —N(R 6 ) 2 , —C(O)OR 6 , or —C(O)N(R 6 ) 2 ), or a straight or branched alkenylene chain (optionally substituted by hydroxy, mercapto, alkylthio, aryl, cycloalkyl, —N(R 6 ) 2 , —C(O)OR 6 , or —C(O)N(R 6 ) 2 );    each R 8  is independently alkyl, alkenyl, aryl, aralkyl or aralkenyl; and    R 9  is —R 7 N(R 5 )C(O)OR 8 , haloalkyl, alkyl (optionally substituted by hydroxy, alkoxy, aralkoxy, haloalkoxy, cyano, nitro, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), alkenyl (optionally substituted by hydroxy, alkoxy, haloalkoxy, cyano, nitro, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), aryl (optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), aralkyl (wherein the aryl group is optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), aralkenyl (wherein the aryl group is optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), or N-heterocyclyl (optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ).    
   
   
       15 . The method of  claim 14  wherein: 
 R 1  is hydrogen;    R 2  is —P(O)(OR 5 )—R 7 —N(R 5 )—S(O) 2 —R 9 ;    R 3  is tetrazole, —C(O)OR 6 , or —C(O)O—R 7 —OC(O)R 5 ;    R 4  is aryl optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, nitro, cyano, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 ; —R 7 —N(R 6 )—C(O)OR 8 , and —N(R 5 )—C(NR 5 )—N(R 5 ) 2 ;    each R 5  is independently hydrogen, alkyl or aralkyl;    each R 6  is independently hydrogen, alkyl, alkenyl, alkynyl, aryl, aralkyl or aralkenyl;    each R 7  is independently a straight or branched alkylene chain (optionally substituted by hydroxy, mercapto, alkylthio, aryl, cycloalkyl, —N(R 6 ) 2 , —C(O)OR 6 , or —C(O)N(R 6 ) 2 ),    each R 8  is independently alkyl, alkenyl, aryl, aralkyl or aralkenyl; and    R 9  is —R 7 N(R 6 )C(O)OR 8 , haloalkyl, alkyl (optionally substituted by hydroxy, alkoxy, aralkoxy, haloalkoxy, cyano, nitro, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), alkenyl (optionally substituted by hydroxy, alkoxy, haloalkoxy, cyano, nitro, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), aryl (optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), aralkyl (wherein the aryl group is optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), aralkenyl (wherein the aryl group is optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), or N-heterocyclyl (optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ).    
   
   
       16 . The method of  claim 15  wherein: 
 R 1  is hydrogen;    R 2  is —P(O)(OR 5 )—R 7 —N(R 5 )—S(O) 2 —R 9 ;    R 3  is tetrazole, —C(O)OR, or —C(O)O—R 7 —OC(O)R 5 ;    R 4  is aryl optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, nitro, cyano, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 ; —R 7 —N(R 6 )—C(O)OR 8 , and —N(R 5 )—C(NR 5 )—N(R 5 ) 2 ;    each R 5  is independently hydrogen, alkyl or aralkyl;    each R 6  is independently hydrogen, alkyl, alkenyl, alkynyl, aryl, aralkyl or aralkenyl;    each R 7  is independently a straight or branched alkylene chain optionally substituted by hydroxy, mercapto, alkylthio, aryl, cycloalkyl, —N(R 6 ) 2 , —C(O)OR 6 , or —C(O)N(R 6 ) 2 ,    each R 8  is independently alkyl, alkenyl, aryl, aralkyl or aralkenyl; and    R 9  is alkyl (optionally substituted by hydroxy, alkoxy, aralkoxy, haloalkoxy, cyano, nitro, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), alkenyl (optionally substituted by hydroxy, alkoxy, haloalkoxy, cyano, nitro, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), aralkyl (wherein the aryl group is optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), or aralkenyl (wherein the aryl group is optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ).    
   
   
       17 . The method of  claim 16  wherein the compound of formula (I) is selected from the group consisting of: 
 2-(3-(amino)methylphenyl)-3-((1-(3-phenylpropylsulfonyl)amino-2-methylpropyl)-(hydroxy)phosphinoyl)propanoic acid, methyl ester;    2-(3-(t-butoxycarbonylamino)methylphenyl)-3-((1-(3-phenylpropylsulfonyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)propanoic acid;    2-(3-(t-butoxycarbonylamino)methylphenyl)-3-((1-(3-phenylpropylsulfonyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)propanoic acid, methyl ester;    2-(3-(amino)methylphenyl)-3-((1-(3-phenylpropylsulfonyl)amino-2-methylpropyl)-(hydroxy)phosphinoyl)propanoic acid;    (2R)-2-(3-(amino)methylphenyl)-3-(((1R)-1-(3-phenylpropylsulfonyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)propanoic acid;    (2S)-2-(3-(amino)methylphenyl)-3-(((1R)-1-(3-phenylpropylsulfonyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)propanoic acid;    (2R/S)-2-(3-(amino)methylphenyl)-3-(((1S)-1-(3-phenylpropylsulfonyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)propanoic acid;    (2R/S)-2-(3-(amino)methylphenyl)-3-(((1R)-1-(3-phenylpropylsulfonyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)propanoic acid;    (2R)-2-(3-(amino)methylphenyl)-3-(((1S)-1-(3-phenylpropylsulfonyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)propanoic acid;    (2S)-2-(3-(amino)methylphenyl)-3-(((1S)-1-(3-phenylpropylsulfonyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)propanoic acid;    2-(3-(t-butoxycarbonylamino)methylphenyl)-3-((1-(3-phenylpropylsulfonyl)amino-2-methylpropyl)(ethoxy)phosphinoyl)propanoic acid, t-butyl ester;    2-(3-(amino)methylphenyl)-3-((1-(2-phenylethylsulfonyl)amino-2-methylpropyl)-(hydroxy)phosphinoyl)propanoic acid;    2-(3-(amino)methylphenyl)-3-((1-(benzylsulfonyl)amino-2-methylpropyl)-(hydroxy)phosphinoyl)propanoic acid;    2-(3-(amino)methylphenyl)-3-((1-(2-(naphth-1-yl)ethylsulfonyl)amino-2-methylpropyl)-(hydroxy)phosphinoyl)propanoic acid;    2-(3-(amino)methylphenyl)-3-((1-(3-(4-methoxyphenyl)propylsulfonyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)propanoic acid;    2-(3-(amino)methylphenyl)-3-((1-(2-(4-methoxyphenyl)ethylsulfonyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)propanoic acid;    2-(3-(amino)methylphenyl)-3-((1-(methylsulfonyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)propanoic acid;    2-(3-(amino)methylphenyl)-3-((1-(2-benzyloxyethylsulfonyl)amino-2-methylpropyl)-(hydroxy)phosphinoyl)propanoic acid;    2-(3-(amino)methylphenyl)-3-((1-(2-hydroxyethylsulfonyl)amino-2-methylpropyl)-(hydroxy)phosphinoyl)propanoic acid;    2-(3-aminophenyl)-3-((1-(3-phenylpropylsulfonyl)amino-2-methylpropyl)-(hydroxy)phosphinoyl)propanoic acid;    2-(3-guanidinophenyl)-3-((1-(3-phenylpropylsulfonyl)amino-2-methylpropyl)(hydroxy)-phosphinoyl)propanoic acid;    2-(3-(amino)methylphenyl)-3-((1-(4-phenylbutylsulfonyl)amino-2-methylpropyl)-(hydroxy)phosphinoyl)propanoic acid, and    2-(3-(amino)methylphenyl)-3-((1-(2-phenylethenylsulfonyl)amino-2-methylpropyl)-(hydroxy)phosphinoyl)propanoic acid.    
   
   
       18 . The method of  claim 15  wherein: 
 R 1  is hydrogen;    R 2  is —P(O)(OR 5 )—R 7 —N(R 5 )—S(O) 2 —R 9 ;    R 3  is tetrazole, —C(O)OR 6 , or —C(O)O—R 7 —OC(O)R 5 ;    R 4  is aryl optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, nitro, cyano, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 ; —R 7 —N(R 6 )—C(O)OR 8 , and —N(R 5 )—C(NR 5 )—N(R 5 ) 2 ;    each R 5  is independently hydrogen, alkyl or aralkyl;    each R 6  is independently hydrogen, alkyl, alkenyl, alkynyl, aryl, aralkyl or aralkenyl;    each R 7  is independently a straight or branched alkylene chain optionally substituted by hydroxy, mercapto, alkylthio, aryl, cycloalkyl, —N(R 6 ) 2 , —C(O)OR 6 , or —C(O)N(R 6 ) 2 ,    each R 8  is independently alkyl, alkenyl, aryl, aralkyl or aralkenyl; and    R 9  is aryl (optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ).    
   
   
       19 . The method of  claim 18  wherein the compound of formula (I) is selected from the group consisting of: 
 2-(3-(amino)methylphenyl)-3-((1-(naphth-1-ylsulfonyl)amino-2-methylpropyl)(hydroxy)-phosphinoyl)propanoic acid;    2-(3-(amino)methylphenyl)-3-((1-(3-trifluoromethylphenylsulfonyl)amino-2-methyl-propyl)(hydroxy)phosphinoyl)propanoic acid;    2-(3-(amino)methylphenyl)-3-((1-(4-pentylphenylsulfonyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)propanoic acid;    2-(3-(amino)methylphenyl)-3-((1-(4-acetamidophenylsulfonyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)propanoic acid;    2-(3-(amino)methylphenyl)-3-((1-(4-phenylphenylsulfonyl)amino-2-methylpropyl)-(hydroxy)phosphinoyl)propanoic acid; and    2-(3-(amino)methylphenyl)-3-((1-(phenylsulfonyl)amino-2-methylpropyl)(hydroxy)-phosphinoyl)propanoic acid.    
   
   
       20 . The method of  claim 15  wherein: 
 R 1  is hydrogen;    R 2  is —P(O)(OR 5 )—R 7 —N(R 5 )—S(O) 2 —R 9 ;    R 3  is tetrazole, —C(O)OR 6 , or —C(O)O—R 7 —OC(O)R 5 ;    R 4  is aryl optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, nitro, cyano, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 ; —R 7 —N(R 6 )—C(O)OR 8 , —N(R 6 )—C(O)—R 6 , —R 7 —N(R 6 )—C(O)—R 6 , and —N(R 5 )—C(NR 5 )—N(R 5 ) 2 ;    each R 5  is independently hydrogen, alkyl or aralkyl;    each R 6  is independently hydrogen, alkyl, alkenyl, alkynyl, aryl, aralkyl or aralkenyl;    each R 7  is independently a straight or branched alkylene chain (optionally substituted by hydroxy, mercapto, alkylthio, aryl, cycloalkyl, —N(R 6 ) 2 , —C(O)OR 6 , or —C(O)N(R 6 ) 2 ),    each R 8  is independently alkyl, alkenyl, aryl, aralkyl or aralkenyl; and    R 9  is —R 7 —N(R 6 )—C(O)OR 8 .    
   
   
       21 . The method of  claim 20  wherein the compound of formula (I) is 2-(3-(amino)methylphenyl)-3-((1-(3-phenyl-2-(benzyloxycarbonyl)aminopropylsulfonyl)-amino-2-methylpropyl)(hydroxy)phosphinoyl)propanoic acid.  
   
   
       22 . The method of  claim 15  wherein: 
 R 1  is hydrogen;    R 2  is —P(O)(OR 5 )—R 7 —N(R 5 )—S(O) 2 —R 9 ;    R 3  is tetrazole, —C(O)OR 6 , or —C(O)O—R 7 —OC(O)R 5 ;    R 4  is aryl optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, nitro, cyano, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 ; —R 7 —N(R 6 )—C(O)OR 8 , —N(R 6 )—C(O)—R 6 , —R 7 —N(R 6 )—C(O)—R 6 , and —N(R 5 )—C(NR 5 )—N(R 5 ) 2 ;    each R 5  is independently hydrogen, alkyl or aralkyl;    each R 6  is independently hydrogen, alkyl, alkenyl, alkynyl, aryl, aralkyl or aralkenyl;    each R 7  is independently a straight or branched alkylene chain (optionally substituted by hydroxy, mercapto, alkylthio, aryl, cycloalkyl, —N(R 6 ) 2 , —C(O)OR 6 , or —C(O)N(R 6 ) 2 ),    each R 8  is independently alkyl, alkenyl, aryl, aralkyl or aralkenyl; and    R 9  is N-heterocyclyl (optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ).    
   
   
       23 . The method of  claim 22  wherein the compound of formula (I) is selected from the group consisting of: 
 2-(3-(amino)methylphenyl)-3-((1-(thien-2-ylsulfonyl)amino-2-methylpropyl)-(hydroxy)phosphinoyl)propanoic acid; and    2-(3-(amino)methylphenyl)-3-((1-(benzothiadiazolylsulfonyl)amino-2-methylpropyl)-(hydroxy)phosphinoyl)propanoic acid.    
   
   
       24 . The method of  claim 1  wherein: 
 R 1  is hydrogen;    R 2  is —P(O)(OR 5 )—R 7 —N(R 5 )—C(O)OR 8 ;    R 3  is —C(O)OR 6 ;    R 4  is unsubstituted phenyl or unsubstituted N-heterocyclyl;    each R 5  is independently hydrogen, alkyl or aralkyl;    each R 6  is independently hydrogen, alkyl, alkenyl, alkynyl, aryl, aralkyl or aralkenyl;    each R 7  is a straight or branched alkylene chain optionally substituted by aryl, —N(R 6 ) 2  or —C(O)OR 6 ; and    R 8  is alkyl, alkenyl, aryl, aralkyl or aralkenyl.    
   
   
       25 . The method of  claim 24  wherein the compound of formula (I) is selected from the group consisting of: 
 2-phenyl-3-(1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)-propanoic acid; and    2-tetrahydroisoquinolinyl-3-((1-(benzyloxycarbonyl)amino-2-methylpropyl)-(hydroxy)phosphinoyl)propanoic acid.    
   
   
       26 . A method of treating pulmonary fibrosis comprising administering a therapeutically effective amount of a compound of formula (II) to a patient in need thereof:  
     
       
         
         
             
             
         
       
     
     wherein: 
 R 1  is hydrogen, alkyl, alkenyl, aryl or aralkenyl;  
 R 2  is —P(O)(OR 5 ) 2 , —P(O)(OR 5 )R 6 , —P(O)(OR 5 )—R 7 —N(R 6 ) 2 , —P(O)(OR 5 )—R 7 —C(O)—R 8 , —P(O)(OR 5 )—R 7 —N(R 5 )—C(O)OR 8 , —P(O)(OR 5 )—R 7 —N(R 5 )—C(O)—R 7 —N(R 5 )—C(O)OR 8 , —P(O)(OR 5 )—R 7 —N(R 5 )—S(O) 2 —R 9 , or —P(O)(OR 5 )—R 7 —N(R 5 )—C(S)—N(R 6 ) 2 ;  
 R 3  is tetrazole, —C(O))R 6 , —C(O)O—R 7 —OC(O)R 5 , —S(O)OR 5 , —S(O) 2 OR 5 , —P(O)(OR 5 ) 2 , —P(O)(OR 5 )R 6 , or —B(OR 5 ) 2 ;  
 R 4  is aryl optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, haloalkoxy, mercapto, alkylthio, phenyl, cycloalkyl, nitro, cyano, —OR 6 , —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 , —R 7 —N(R 6 )—C(O)OR 8 , —N(R 6 )—C(O)—R 6 , —R 7 —N(R 6 )—C(O)—R 6 , —C(O)—N(R 6 ) 2 , —C(O)—R 7 —N(R 6 ) 2 , —N(R 5 )—C(NR 5 )—N(R 5 ) 2 , —N(R 5 )—C(O)—N(R 6 ) 2  and —N(R 5 )—C(O)—R 7 —N(R 6   2 );  
 or R 4  is N-heterocyclyl wherein a carbon atom in the N-heterocyclyl may be optionally substituted by alkyl, halo, nitro, cyano, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 , —R 7 —N(R 6 )—C(O)OR 8 , —N(R 6 )—C(O)—R 6 , —R 7 —N(R 6 )—C(O)—R 6 , —C(O)—N(R 6 ) 2 , —C(O)—R 7 —N(R 6 ) 2 , —N(R 5 )—C(NR 5 )—N(R 5 ) 2 , —N(R 5 )—C(O)—N(R 6 ) 2  or —N(R 5 )—C(O)—R 7 —N(R 6   2 ), or wherein a nitrogen atom in the N-heterocyclyl may be optionally substituted by —C(NR 5 )—N(R 5 ) 2 , —C(NR 5 )—R 6 , —C(O)—N(R 6 ) 2  or —C(O)—R 7 —N(R 6 ) 2 ;  
 each R 5  is independently hydrogen, alkyl or aralkyl;  
 each R 6  is independently hydrogen, alkyl, alkenyl, alkynyl, aryl, aralkyl or aralkenyl;  
 each R 7  is independently cycloalkylene (optionally substituted by alkyl), a straight or branched alkylene chain (optionally substituted by hydroxy, mercapto, alkylthio, aryl, cycloalkyl, —N(R 6 ) 2 , —C(O)OR , or —C(O)N(R 6 ) 2 ), or a straight or branched alkenylene chain (optionally substituted by hydroxy, mercapto, alkylthio, aryl, cycloalkyl, —N(R 6 ) 2 , —C(O)OR 6 , or —C(O)N(R 6 ) 2 );  
 each R 8  is independently alkyl, alkenyl, aryl, aralkyl or aralkenyl; and  
 R 9  is —R 7 N(R 6 )C(O)OR 8 , haloalkyl, alkyl (optionally substituted by hydroxy, alkoxy, aralkoxy, haloalkoxy, cyano, nitro, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), alkenyl (optionally substituted by hydroxy, alkoxy, haloalkoxy, cyano, nitro, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), aryl (optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), aralkyl (wherein the aryl group is optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), aralkenyl (wherein the aryl group is optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), or N-heterocyclyl (optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 );  
 provided that when R 3  is —C(O)OH or when R 4  is a substituted aryl or substituted N-heterocyclyl, R 2  can not be —P(O)(OR 5 )—R 7 —N(H)—C(O)OR 8  or —P(O)(OR 5 )—R 7 —N(H)—C(O)—R 7 —N(R 5 )—C(O)OR 8 ;  
 as a single stereoisomer, a mixture of stereoisomers, or as a racemic mixture of stereoisomers; or a pharmaceutically acceptable salt thereof.  
 
   
   
       27 . The method of  claim 26  wherein: 
 R 1  is hydrogen;    R 2 —P(O)(OR 5 )R 6 , —P(O)(OR 5 )—R 7 —N(R 6 ) 2 , or —P(O)(OR 5 )—R 7 —N(R 5 )—C(S)—N(R 6 ) 2 ;    R 3  is tetrazole, —C(O)OR 6  or —C(O)O—R 7 —OC(O)R 5 ;    R 4  is aryl optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, nitro, cyano, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 , —R 7 —N(R 6 )—C(O)R 8 , —N(R 6 )—C(O)—R 6 , —R 7 —N(R 6 )—C(O)—R 6 , —C(O)—N(R 6 ) 2 , —C(O)—R 7 —N(R 6 ) 2 , —N(R 5 )—C(NR 5 )—N(R 5 ) 2 , —N(R 5 )—C(O)—N(R 6 ) 2  and —N(R 5 )—C(O)—R 7 —N(R 6   2 );    each R 5  is independently hydrogen, alkyl or aralkyl;    each R 6  is independently hydrogen, alkyl, alkenyl, alkynyl, aryl, aralkyl or aralkenyl;    each R 7  is a straight or branched alkylene chain (optionally substituted by hydroxy, mercapto, alkylthio, aryl, cycloalkyl, —N(R 6 ) 2 , —C(O)OR 6 , or —C(O)N(R 6 ) 2 ); and    each R 8  is independently alkyl, alkenyl, aryl, aralkyl or aralkenyl.    
   
   
       28 . The method of  claim 27  wherein the compound of formula (II) is selected from the group consisting of: 
 2-(3-guanidinophenyl)-2-((1-(2-phenylethyl)amino-2-methylpropyl)-(hydroxy)phosphinoyloxy)ethanoic acid;    2-(3-aminophenyl)-2-((phenyl)(hydroxy)phosphinoyloxy)ethanoic acid;    2-(3-guanidinophenyl)-2-((1-amino-2-methylpropyl)(hydroxy)phosphinoyloxy)ethanoic acid; and    2-(3-guanidinophenyl)-2-((1-(benzylaminothiocarbonyl)amino-2-methylpropyl)-(hydroxy)phosphinoyloxy)ethanoic acid.    
   
   
       29 . The method of  claim 26  wherein: 
 R 1  is hydrogen;    R 2  is —P(O)(OR 5 )—R 7 —N(R 5 )—S(O) 2 —R 9 ;    R 3  is tetrazole, —C(O)OR 6  or —C(O)O—R 7 —OC(O)R 5 ;    R 4  is aryl optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, nitro, cyano, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 , —R 7 —N(R 6 )—C(O)OR 8 , —N(R 6 )—C(O)—R 6 , —R 7 —N(R 6 )—C(O)—R 6 , —C(O)—N(R 6 ) 2 , —C(O)—R 7 —N(R 6 ) 2 , —N(R 5 )—C(NR 5 )—N(R 5 ) 2 , —N(R 5 )—C(O)—N(R 6 ) 2  and —N(R 5 )—C(O)—R 7 —N(R 6   2 );    each R 5  is independently hydrogen, alkyl or aralkyl;    each R 6  is independently hydrogen, alkyl, alkenyl, alkynyl, aryl, aralkyl or aralkenyl;    each R 7  is a straight or branched alkylene chain (optionally substituted by hydroxy, mercapto, alkylthio, aryl, cycloalkyl, —N(R 6 ) 2 , —C(O)OR 6 , or —C(O)N(R 6 ) 2 );    each R 8  is independently alkyl, alkenyl, aryl, aralkyl or aralkenyl; and    R 9  is alkyl (optionally substituted by hydroxy, alkoxy, aralkoxy, haloalkoxy, cyano, nitro, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), alkenyl (optionally substituted by hydroxy, alkoxy, haloalkoxy, cyano, nitro, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), aralkyl (wherein the aryl group is optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR 5 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), or aralkenyl (wherein the aryl group is optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ).    
   
   
       30 . The method of  claim 29  wherein the compound of formula (II) is selected from the group consisting of: 
 2-(3-guanidinophenyl)-2-((1-(benzylsulfonyl)amino-2-methylpropyl)(hydroxy)-phosphinoyloxy)ethanoic acid; and    2-(3-guanidinophenyl)-2-((1-(2-phenylethenylsulfonyl)amino-2-methylpropyl)-(hydroxy)phosphinoyloxy)ethanoic acid.    
   
   
       31 . The method of  claim 26  wherein: 
 R 1  is hydrogen;    R 2  is —P(O)(OR 5 ) 2 , —P(O)(OR 5 )R 6 , —P(O)(OR 5 )—R 7 —N(R 6 ) 2 , —P(O)(OR 5 )—R 7 —C(O)—R 8 , —P(O)(OR 5 )—R 7 —N(R 5 )—C(O)OR 8 , —P(O)(OR 5 )—R 7 —N(R 5 )—C(O)—R 7 —N(R 5 )—C(O)OR 8 , —P(O)(OR 5 )—R 7 —N(R 5 )—S(O) 2 —R 9 , or —P(O)(OR 5 )—R 7 —N(R 5 )—C(S)—N(R 6 ) 2 ;    R 3  is tetrazole;    R 4  is aryl optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, nitro, cyano, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 , —R 7 —N(R 6 )—C(O)OR 8 , —N(R 6 )—C(O)—R 6 , —R 7 —N(R 6 )—C(O)—R 6 , —C(O)—N(R 6 ) 2 , —C(O)—R 7 —N(R 6 ) 2 , —N(R 5 )—C(NR 5 )—N(R 5 ) 2 , —N(R 5 )—C(O)—N(R 6 ) 2  and —N(R 5 )—C(O)—R 7 —N(R 6   2 );    or R 4  is N-heterocyclyl wherein a carbon atom in the N-heterocyclyl may be optionally substituted by alkyl, halo, nitro, cyano, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 , —R 7 —N(R 6 )—C(O)OR 8 , —N(R 6 )—C(O)—R 6 , —R 7 —N(R 6 )—C(O)—R 6 , —C(O)—N(R 6 ) 2 , —C(O)—R 7 —N(R 6 ) 2 , —N(R 5 )—C(NR 5 )—N(R 5 ) 2 , —N(R 5 )—C(O)—N(R 6 ) 2  or —N(R 5 )—C(O)—R 7 —N(R 2 ), or wherein a nitrogen atom in the N-heterocyclyl may be optionally substituted by —C(NR 5 )—N(R 5 ) 2 , —C(NR 5 )—R 6 , —C(O)—N(R 6 ) 2  or —C(O)—R 7 —N(R 6 ) 2 ;    each R 5  is independently hydrogen, alkyl or aralkyl;    each R 6  is independently hydrogen, alkyl, alkenyl, alkynyl, aryl, aralkyl or aralkenyl;    each R 7  is independently cycloalkylene (optionally substituted by alkyl), a straight or branched alkylene chain (optionally substituted by hydroxy, mercapto, alkylthio, aryl, cycloalkyl, —N(R 6 ) 2 , —C(O)OR 6 , or —C(O)N(R 6 ) 2 ), or a straight or branched alkenylene chain (optionally substituted by hydroxy, mercapto, alkylthio, aryl, cycloalkyl, —N(R 6 ) 2 , —C(O)OR 6 , or —C(O)N(R 6 ) 2 );    each R 8  is independently alkyl, alkenyl, aryl, aralkyl or aralkenyl; and    R 9  is —R 7 N(R 6 )C(O)OR 8 , haloalkyl, alkyl (optionally substituted by hydroxy, alkoxy, aralkoxy, haloalkoxy, cyano, nitro, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), alkenyl (optionally substituted by hydroxy, alkoxy, haloalkoxy, cyano, nitro, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), aryl (optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), aralkyl (wherein the aryl group is optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), aralkenyl (wherein the aryl group is optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ), or N-heterocyclyl (optionally substituted by alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halo, haloalkoxy, —N(R 6 ) 2 , —C(O)OR 6 , —C(O)N(R 6 ) 2  or —N(R 6 )C(O)R 6 ).    
   
   
       32 . The method of  claim 31  wherein the compound of formula (II) is 2-methyl-1-[1-(3-guanidinophenyl)-1-tetrazolylmethoxy](hydroxy)phosphinoyl-propylcarbamic acid, benzyl ester.  
   
   
       33 . A method of treating pulmonary fibrosis comprising administering a therapeutically effective amount of a compound of formula (III) to a patient in need thereof:  
     
       
         
         
             
             
         
       
     
     wherein: 
 X is —CH 2 — or —O—;  
 R 1  is hydrogen, alkyl, alkenyl, aryl or aralkenyl;  
 R 2  is —P(O)(OR 5 )—R 7 —N(R 5 )—C(O)R 6 , —P(O)(OR 5 )—R 7 —N(R 5 )—C(O)OR 8  or —P(O)(OR 5 )—R 7 —N(R 5 )—C(O)—R 7 —N(R 5 )—C(O)OR 8 ,  
 R 3  is —C(O)OH;  
 R 4  is aryl optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, haloalkoxy, mercapto, alkylthio, phenyl, cycloalkyl, nitro, cyano, —OR 6 , —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 , —R 7 —N(R 6 )—C(O)OR 8 , —N(R 6 )—C(O)—R 6 , —R 7 —N(R 6 )—C(O)—R 6 , —C(O)—N(R 6 ) 2 , —C(O)—R 7 —N(R 6 ) 2 , —N(R 5 )—C(NR 5 )—N(R 5 ) 2 , —N(R 5 )—C(O)—N(R 6 ) 2  and —N(R 5 )—C(O)—R 7 —N(R 6   2 );  
 or R 4  is N-heterocyclyl wherein a carbon atom in the N-heterocyclyl may be optionally substituted by alkyl, halo, nitro, cyano, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 , —R 7 —N(R 6 )—C(O)OR 8 , —N(R 6 )—C(O)—R 6 , —R 7 —N(R 6 )—C(O)—R 6 , —C(O)—N(R 6 ) 2 , —C(O)—R 7 —N(R 6 ) 2 , —N(R 5 )—C(NR 5 )—N(R 5 ) 2 , —N(R 5 )—C(O)—N(R 6 ) 2  or —N(R 5 )—C(O)—R 7 —N(R 6   2 ), or wherein a nitrogen atom in the N-heterocyclyl may be optionally substituted by —C(NR 5 )—N(R 5 ) 2 , —C(NR 5 )—R 6 , —C(O)—N(R 6 ) 2  or —C(O)—R 7 —N(R 6 ) 2 ;  
 each R 5  is independently hydrogen, alkyl or aralkyl;  
 each R 6  is independently hydrogen, alkyl, alkenyl, alkynyl, aryl, aralkyl or aralkenyl;  
 each R 7  is independently cycloalkylene (optionally substituted by alkyl), a straight or branched alkylene chain (optionally substituted by hydroxy, mercapto, alkylthio, aryl, cycloalkyl, —N(R 6 ) 2 , —C(O)OR 6 , or —C(O)N(R 6 ) 2 ), or a straight or branched alkenylene chain (optionally substituted by hydroxy, mercapto, alkylthio, aryl, cycloalkyl, —N(R 6 ) 2 , —C(O)OR 6 , or —C(O)N(R 6 ) 2 ); and  
 each R 8  is independently alkyl, alkenyl, aryl, aralkyl or aralkenyl;  
 as a single stereoisomer, a mixture of stereoisomers, or as a racemic mixture of stereoisomers; or a pharmaceutically acceptable salt thereof.  
 
   
   
       34 . The method of  claim 33  wherein: 
 X is —O—;    R 2  is —P(O)(OR 5 )—R 7 —N(R 5 )—C(O)OR 8 ; and    R 4  is aryl optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, nitro, cyano, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 , —R 7 —N(R 6 )—C(O)OR 8 , —N(R 6 )—C(O)—R 6 , —R 7 —N(R 6 )—C(O)—R 6 , —C(O)—N(R 6 ) 2 , —C(O)—N(R 6 )—N(R 6 ) 2 , —C(O)—R 7 —N(R 6 ) 2 , —N(R 5 )—C(NR 5 )—N(R 5 ) 2 , —N(R 5 )—C(O)—N(R 6 ) 2  and —N(R 5 )—C(O)—R 7 —N(R 6   2 ).    
   
   
       35 . The method of  claim 34  wherein the compound of formula (III) is selected from the group consisting of: 
 2-(3-guanidinophenyl)-2-((1-(benzyloxycarbonyl)aminoethyl)(hydroxy)-phosphinoyloxy)ethanoic acid;    2-(3-guanidinophenyl)-2-(((benzyloxycarbonyl)aminomethyl)(hydroxy)-phosphinoyloxy)ethanoic acid;    2-(3-guanidinophenyl)-2-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyloxy)ethanoic acid;    2-(3-guanidinophenyl)-2-((1-(benzyloxycarbonyl)aminohexyl)-(hydroxy)phosphinoyloxy)ethanoic acid;    2-(3-aminophenyl)-2-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyloxy)ethanoic acid;    2-(3-guanidinophenyl)-2-((1-(benzyloxycarbonyl)amino-3-methylbutyl)(hydroxy)phosphinoyloxy)ethanoic acid;    2-(2-chloro-3-guanidinophenyl)-2-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyloxy)ethanoic acid;    2-(3-guanidinophenyl)-2-((1-(benzyloxycarbonyl)amino-1-phenylmethyl)(hydroxy)phosphinoyloxy)ethanoic acid;    2-(2-fluoro-3-guanidinophenyl)-2-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyloxy)ethanoic acid;    2-(3-guanidinophenyl)-2-((1-(benzyloxycarbonyl)amino-1-cyclohexylmethyl)(hydroxy)phosphinoyloxy)ethanoic acid;    2-(2-methyl-3-guanidinophenyl)-2-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyloxy)ethanoic acid;    2-(3-(amino)methylphenyl)-2-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyloxy)ethanoic acid;    2-(3-(guanidinomethyl)phenyl)-2-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyloxy)ethanoic acid;    2-(3-(1-iminoethylaminophenyl))-2-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyloxy)ethanoic acid;    2-(3-(t-butoxycarbonylamino)methylphenyl)-2-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyloxy)ethanoic acid;    2-(3-(ethoxycarbonylamino)methylphenyl)-2-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyloxy)ethanoic acid;    2-(3-(isopropoxycarbonylamino)methylphenyl)-2-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyloxy)ethanoic acid;    2-(3-(2,2-dimethylpropylcarbonylamino)methylphenyl)-2-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyloxy)ethanoic acid;    2-(3-guanidinophenyl)-2-((1-(2-phenylethylcarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyloxy)ethanoic acid; and    2-(3-guanidinophenyl)-2-((1-(2-phenylethenylcarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyloxy)ethanoic acid.    
   
   
       36 . The method of  claim 33  wherein: 
 X is —O—;    R 2  is —P(O)(OR 5 )—R 7 —N(R 5 )—C(O)—R 7 —N(R 5 )—C(O)OR 8 ; and    R 4  is aryl optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, nitro, cyano, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 , —R 7 —N(R 6 )—C(O)OR 8 , —N(R 6 )—C(O)—R 6 , —R 7 —N(R 6 )—C(O)—R 6 , —C(O)—N(R 6 ) 2 , —C(O)—N(R 6 )—N(R 6 ) 2 , —C(O)—R 7 —N(R 6 ) 2 , —N(R 5 )—C(NR 5 )—N(R 5 ) 2 , —N(R 5 )—C(O)—N(R 6 ) 2  and —N(R 5 )—C(O)—R 7 —N(R 6   2 ).    
   
   
       37 . The method of  claim 36  wherein the compound of formula (III) is selected from the group consisting of: 
 2-(3-guanidinophenyl)-2-[(1-(1-benzyloxycarbonylamino-2-(4-hydroxyphenyl)-ethylcarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyloxy]ethanoic acid;    2-(3-guanidinophenyl)-2-[(1-(1-benzyloxycarbonylamino-2-phenylethylcarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyloxy]ethanoic acid;    2-(2-fluoro-3-guanidinophenyl)-2-[(1-(1-benzyloxycarbonylamino-2-phenylethylcarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyloxy]ethanoic acid;    2-(3-guanidinophenyl)-2-[(1-(1-phenylcarbonylamino-2-phenylethylcarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyloxy]ethanoic acid;    2-(3-guanidinophenyl)-2-[(1-(1-ethoxycarbonylamino-2-phenylethylcarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyloxy]ethanoic acid;    2-(3-guanidinophenyl)-2-[(1-(1-benzyloxycarbonylamino-3-phenylpropylcarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyloxy]ethanoic acid; and    2-(3-(amino)methylphenyl)-2-[(1-(1-benzyloxycarbonylamino-3-phenylpropylcarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyloxy]ethanoic acid.    
   
   
       38 . The method of  claim 33  wherein: 
 X is —CH 2 —;    R 2  is —P(O)(OR 5 )—R 7 —N(R 5 )—C(O)R 6  or —P(O)(OR 5 )—R 7 —N(R 5 )—C(O)OR 8 ; and    R 4  is aryl optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, nitro, cyano, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 , —R 7 —N(R 6 )—C(O)OR 8 , —N(R 6 )—C(O)—R 6 , —R 7 —N(R 6 )—C(O)—R 6 , —C(O)—N(R 6 ) 2 , —C(O)—N(R 6 )—N(R 6 ) 2 , —C(O)—R 7 —N(R 6 ) 2 , —N(R 5 )—C(NR 5 )—N(R 5 ) 2 , —N(R 5 )—C(O)-N(R 6 ) 2  and —N(R 5 )—C(O)—R 7 —N(R 6   2 ).    
   
   
       39 . The method of  claim 38  wherein the compound of formula (III) is selected from the group consisting of: 
 2-(3-(amino)methylphenyl)-3-((1-(methylcarbonyl)amino-2-methylpropyl)(hydroxy)-phosphinoyl)propanoic acid;    2-(3-(hydrazinocarbonyl)phenyl)-3-((1-(benzyloxycarbonyl)amino-2-methylpropyl)-(hydroxy)phosphinoyl)propanoic acid;    2-(3-guanidinophenyl)-3-((1-(benzyloxycarbonyl)aminoethyl)(hydroxy)phosphinoyl)-propanoic acid;    2-(3-guanidinophenyl)-3-((1-(benzyloxycarbonyl)amino-3-methylbutyl)(hydroxy)phosphinoyl)propanoic acid;    2-(3-guanidinophenyl)-3-(((benzyloxycarbonyl)aminomethyl)(hydroxy)phosphinoyl)-propanoic acid;    2-(3-guanidinophenyl)-3-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)-phosphinoyl)propanoic acid;    2-(2-chloro-5-guanidinophenyl)-3-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)propanoic acid;    2-(3-(amino)methylphenyl)-3-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)-phosphinoyl)propanoic acid; and    2-(3-(amino)methylphenyl)-3-((1-(2-phenylethylcarbonyl)amino-2-methylpropyl)-(hydroxy)phosphinoyl)propanoic acid.    
   
   
       40 . The method of  claim 33  wherein: 
 X is —CH 2 —;    R 2  is —P(O)(OR 5 )—R 7 —N(R 5 )—C(O)—R 7 —N(R 5 )—C(O)OR 8 ; and    R 4  is aryl optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, nitro, cyano, —N(R 6 ) 2 , —R 7 —N(R 6 ) 2 , —N(R 6 )—C(O)OR 8 , —R 7 —N(R 6 )—C(O)OR 8 , —N(R 6 )—C(O)—R 6 , —R 7 —N(R 6 )—C(O)—R 6 , —C(O)—N(R 6 ) 2 , —C(O)—N(R 6 )—N(R 6 ) 2 , —C(O)—R 7 —N(R 6 ) 2 , —N(R 5 )—C(NR 5 )—N(R 5 ) 2 , —N(R 5 )—C(O)—N(R 6 ) 2  and —N(R 5 )—C(O)—R 7 —N(R 6   2 ).    
   
   
       41 . The method of  claim 40  wherein the compound of formula (III) is selected from the group consisting of: 
 2-(3-guanidinophenyl)-3-(((1-benzyloxycarbonylamino-2-phenylethyl)carbonylaminomethyl)(hydroxy)phosphinoyl)propanoic acid;    2-(3-guanidinophenyl)-3-(((1-benzyloxycarbonylamino-2-phenylethyl)carbonylaminomethyl)(hydroxy)phosphinoyl)propanoic acid.    
   
   
       42 . A method of treating pulmonary fibrosis comprising administering a therapeutically effective amount of a TAFI inhibitor to a patient in need thereof.